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Higher Responsiveness to Rosuvastatin in Polygenic versus Monogenic Hypercholesterolemia: A Propensity Score Analysis

Abstract

Background: The monogenic defect in familial hypercholesterolemia (FH) is detected in ∼40% of cases. The majority of mutation-negative patients have a polygenic cause of high LDL-cholesterol (LDL-C). We sought to investigate whether the underlying monogenic or polygenic defect is associated with the response to rosuvastatin. Methods: FH Individuals were tested for mutations in LDLR and APOB genes. A previously established LDL-C-specific polygenic risk score (PRS) was used to examine the possibility of polygenic hypercholesterolemia in mutation-negative patients. All of the patients received rosuvastatin and they were followed for 8 ± 2 months. A propensity score analysis was performed to evaluate the variables associated with the response to treatment. Results: Monogenic subjects had higher mean (±SD) baseline LDL-C when compared to polygenic (7.6 ± 1.5 mmol/L vs. 6.2 ± 1.2 mmol/L; p < 0.001). Adjusted model showed a lower percentage of change in LDL-C after rosuvastatin treatment in monogenic patients vs. polygenic subjects (45.9% vs. 55.4%, p < 0.001). The probability of achieving LDL-C targets in monogenic FH was lower than in polygenic subjects (0.075 vs. 0.245, p = 0.004). Polygenic patients were more likely to achieve LDL-C goals, as compared to those monogenic (OR 3.28; 95% CI: 1.23-8.72). Conclusion: Our findings indicate an essentially higher responsiveness to rosuvastatin in FH patients with a polygenic cause, as compared to those carrying monogenic mutations.

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Details

Category:
Articles
Type:
artykuły w czasopismach
Published in:
Life no. 10,
ISSN: 0024-3019
Language:
English
Publication year:
2020
Bibliographic description:
Mickiewicz A., Futema M., Ćwiklinska A., Kuchta A., Jankowski M., Kaszubowski M., Chmara M., Wasąg B., Fijałkowski M., Jaguszewski M., Humphries S. E., Gruchała M.: Higher Responsiveness to Rosuvastatin in Polygenic versus Monogenic Hypercholesterolemia: A Propensity Score Analysis// Life -Vol. 10,iss. 5 (2020), s.73-
DOI:
Digital Object Identifier (open in new tab) 10.3390/life10050073
Verified by:
Gdańsk University of Technology

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